A Trial to Find the Safe Dose for BI 891065 Alone and in... | NCT03166631

NCT03166631

ID	Type	Description	Link
2017-000465-74	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part A: 5 mg BI 891065	Experimental	BI 891065 alone	Drug: BI 891065
Part A: 15 mg BI 891065	Experimental	BI 891065 alone	Drug: BI 891065
Part A: 25 mg BI 891065	Experimental	BI 891065 alone	Drug: BI 891065
Part A: 50 mg BI 891065	Experimental	BI 891065 alone	Drug: BI 891065
Part A: 100 mg BI 891065	Experimental	BI 891065 alone	Drug: BI 891065
Part A: 200 mg BI 891065	Experimental	BI 891065 alone	Drug: BI 891065
Part A: 400 mg BI 981065

Name	Type	Description	Arm Group Labels	Other Names
BI 891065	Drug	Part A, Part B	Part A: 100 mg BI 891065 Part A: 15 mg BI 891065 Part A: 200 mg BI 891065 Part A: 25 mg BI 891065

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part A - Maximum Tolerated Dose (MTD) of BI 891065	Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.	First treatment cycle (MTD evaluation period), up to 21 days.
Part A - Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period	DLT is defined as: Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease. Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.	First treatment cycle (MTD evaluation period), up to 21 days.
Part B: Maximum Tolerated Dose (MTD) of BI 891065 in Combination With Ezabenlimab	Maximum tolerated dose (MTD) of BI 891065 in combination with ezabenlimab, defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.	First treatment cycle (MTD evaluation period), up to 21 days.
Part B: Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period	DLT is defined as: Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease. Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.

Secondary Outcomes

Measure	Description	Time Frame
Part A: Number of Patients With Dose-limiting Toxicities (DLT) During the Entire On-treatment Period	DLT is defined as: Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease. Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Provision of signed and dated, written informed consent form (ICF) in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses
Patients ≥18 years-of-age at the time of signature of the ICF
Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control (that result in a low failure rate of less than 1% per year when used consistently and correctly)during trial participation and for at least 6 months after the last administration of trial medication. A list of contraception methods meeting these criteria is provided in the patient information.
Eastern Cooperative Oncology Group (ECOG) score: 0 or 1
Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement
For Parts A and B: Patients with a confirmed diagnosis of advanced, unresectable and/or metastatic solid tumours, who have failed standard treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies. Measurable lesions according to RECIST Version 1.1 must be present. Eligibility is limited to the following tumour subtypes in Part B: bladder, colon, breast, Non-small cell lung cancer (NSCLC), ovarian, pancreatic, renal, esophagogastric, sarcoma, prostate, and melanoma.
For Parts B and C: Patients must have measurable disease per RECIST v1.1, must have at least 1 tumour lesion amenable to biopsy, and must be willing to undergo a biopsy prior to first treatment and another biopsy while on therapy unless clinically contraindicated.
For Part C: Patients with metastatic NSCLC who developed disease progression (per RECIST v1.1) after the first scan (where SD, Partial Response (PR), or Complete Response (CR) was demonstrated at the first scan), and require new anti-cancer therapy after first line treatment with an anti programmed cell death protein 1 (PD-1)/anti programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) (given either as single agent therapy or in combination with a platinum-based chemotherapy regimen).

Exclusion criteria:

Major surgery (major according to the Investigator's and/or Medical Monitor's assessment) performed within 12 weeks prior to randomization or planned within 12 months after screening (e.g., hip replacement)
Presence of other active invasive cancers other than the one treated in this trial within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, or in situ carcinoma of uterine cervix, or other local tumours considered cured by local treatment
Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
Previous administration of BI 891065 or BI 754091
Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatments.
Patients who have been treated with any other anticancer drug within 4 weeks or within 5 half-life periods (whichever come earlier) prior to first administration of BI 891065. At least 7 days must have elapsed between the last dose of such agent and the first dose of study drug.
Persistent toxicity from previous treatments that has not resolved to ≤ Grade 1 (except for alopecia and Grade 2 neuropathy due to prior platinum-based therapy)
Active, known or suspected autoimmune disease except vitiligo or resolved asthma/atopy
Interstitial lung disease
Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTcF) >470 msec
- Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting Electrocardiograms (ECGs), e.g., complete left bundle branch block, third degree heart block
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication with known or possible risk of QT interval prolongation
- Patients with an ejection fraction (EF) <55% or the lower limit of normal of the institutional standard will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram [ECHO], multi-gated acquisition scan [MUGA]). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both.
Out of range laboratory values are defined as:
- Alanine transaminase (ALT) and aspartate amino transferase (AST) >3 times the Upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
- Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 times ULN or direct bilirubin >1.5 times ULN
Human immunodeficiency virus (HIV) infection, acute or chronic viral hepatitis
Known hypersensitivity to the trial drugs or their excipients
Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as cardiac, neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator and/or Medical Monitor would make the patient inappropriate for entry into the trial.
Chronic alcohol or drug abuse or any condition that, in the Investigator's and/or Medical Monitor's opinion, makes them an unreliable trial patient or unlikely to complete the trial
Women who are pregnant, nursing, or who plan to become pregnant while in the trial and for at least 6 months after the last administration of trial medication.
Men who plan to father a child while in the trial and for at least 6 months after the last administration of trial medication.
Known presence of symptomatic central nervous system (CNS) metastases, unless asymptomatic and off corticosteroids and/or anti-convulsant therapy for at least 2 weeks prior start of treatment. Patients with asymptomatic CNS metastases may be enrolled following a 2-week washout period.
Patients receiving systemic treatment with any immunosuppressive medication within 1 week prior treatment start (steroids of max. 10 mg prednisolone equivalent per day are allowed, topical and inhaled steroids are not considered as immunosuppressive).
For Parts A and B: Patients with known epidermal growth factor receptor (EGFR), known anaplastic lymphoma kinase (ALK), or known ROS Proto-Oncogene 1 (ROS1) genomic tumour aberrations, unless disease has progressed following available EGFR or ALK targeted therapy (including osimertinib for EGFR T790M-mutated NSCLC)
Out of range lab values as defined:
- Absolute neutrophil count (ANC) <1.5 x 109/L (<1500/mm3)
- Platelet (PLT) count <100 x 109/L
Haemoglobin <90 g/L (<9 g/dL)

-- Creatinine >1.5 times ULN (patients may enter if creatinine is >1.5 x ULN and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2) (Chronic Kidney Disease Epidemiology [CKD-EPI] Collaboration equation); confirmation of eGRF is only required when creatinine is >1.5 X ULN.
For Part C: Patients with EGFR, ALK, or (if known) ROS1 genomic tumor aberrations
For Part C: Patients with any CTLA-4 therapy
For Part C: One or more lines of anti-cancer therapy between previous anti-PD-1/anti-PDL1 mAb therapy and study entry.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Florida Cancer Specialists		Sarasota	Florida	34232	United States
Sarah Cannon Research Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
41408891	Derived	Patel MR, Hamilton EP, George B, Kretschmar G, Harada A, Graeser R, Eleftheraki A, Tachibana Y, Yamamoto N. The Second Mitochondria-Derived Activator of Caspases Mimetic BI 891065 in Patients With Advanced Solid Tumors: Results From Two Phase I Studies. Cancer Med. 2025 Dec;14(24):e71451. doi: 10.1002/cam4.71451.

Label	URL
Related Info	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 12, 2020	May 14, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Part A: 400 mg BI 981065

Part A: 5 mg BI 891065

Part A: 50 mg BI 891065

Part B: 200 mg BI 891065 QD + 240 mg BI 754091

Part B: 200 mg BI 981065 BID + 240 mg BI 754091

Part B: 50 mg BI 891065 QD + 240 mg BI 754091

Treated Set (TS) (Part A): The TS (Part A) included all patients who received at least one dose of BI 891065.

Treated Set (TS) (Part B): The TS (Part B) included all patients who received at least one dose of BI 891065 or BI 754091.

Arm/Group Information

ID	Title	Description
BG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
BG001	Part A: 15 mg BI 891065	3 film-coated tablets of 5 mg (15 mg total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
BG002	Part A: 25 mg BI 891065	1 film-coated tablet of 5 mg plus 1 film-coated tablet of 20 mg (25 mg in total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
BG003	Part A: 50 mg BI 891065	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
BG004	Part A: 100 mg BI 891065	2 film-coated tablets of 50 mg (100 mg in total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
BG005	Part A: 200 mg BI 891065	4 film-coated tablets of 50 mg of BI 891065 (200 mg in total) were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
BG006	Part A: 400 mg BI 891065	8 film-coated tablets of 50 mg (400 mg in total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
BG007	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
BG008	Part B: 200 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 50 mg, or 2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
BG009	Part B: 400 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 100 mg (400 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
BG010	Part B: 200 mg BI 891065 BID + 240 mg BI 754091	2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally twice daily (BID) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
BG011	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Treated Set.

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00076.0± 2.6 BG00158.0± NASince only 1 patients was analyzed no standard deviation is available. BG00265.7± 5.5

Sex: Female, Male

Treated Set

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0010 BG002

Ethnicity (NIH/OMB)

Treated Set.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Treated Set.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part A - Maximum Tolerated Dose (MTD) of BI 891065

Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.

MTD Evaluation Set (Part A): All patients who received BI 891065 and completed the safety assessments required during cycle 1 or who experienced a DLT during cycle 1.

Posted

Number

Milligram

First treatment cycle (MTD evaluation period), up to 21 days.

ID	Title	Description
OG000	Part A: BI 891065	Film-coated tablets of BI 891065 (dose level 5 mg, 15 mg, 25 mg, 50 mg, 100 mg, 200 mg or 400 mg) were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Units	Counts
Participants	OG00021

Title

Denominators

Categories

Title	Measurements
	OG000NAThe MTD has not been reached and identified in Part A of this study because of the low number of dose limiting toxicities (DLTs) observed.

Primary

Part A - Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period

DLT is defined as:

Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease.

Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.

MTD Evaluation Set (Part A): All patients who received BI 891065 and completed the safety assessments required during cycle 1 or who experienced a DLT during cycle 1.

Posted

Count of Participants

Participants

First treatment cycle (MTD evaluation period), up to 21 days.

ID	Title	Description
OG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Secondary

Part A: Number of Patients With Dose-limiting Toxicities (DLT) During the Entire On-treatment Period

DLT is defined as:

Treated Set (TS) (Part A): The TS (Part A) included all patients who received at least 1 dose of BI 891065.

Posted

Count of Participants

Participants

From first drug administration until last drug administration plus residual effect period of 30 days, up to 282 days.

ID	Title	Description
OG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Secondary

Part A: Number of Patients With Objective Response (OR)

OR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, defined as the best overall response of complete response (CR) and partial response (PR), where the best overall response is the best time point response recorded from the first administration of study medication until the end of treatment Number of patients with objective response is reported.

Treated Set (TS) (Part A): The TS (Part A) included all patients who received at least 1 dose of BI 891065.

Posted

Count of Participants

Participants

Up to 252 days.

ID	Title	Description
OG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
OG001	Part A: 15 mg BI 891065	3 film-coated tablets of 5 mg (15 mg total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Secondary

Part A: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)

Maximum measured plasma concentration at steady state (cmax,ss) during the first treatment cycle.

Timeframe description:

*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.

**: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.

Pharmacokinetic Parameter Set (PKS) (Part A): All patients in the TS (Part A) who have at least one valid secondary pharmacokinetic (PK) endpoint available. Only patients with available data for this endpoint were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanomol per Liter (nmol/L)

Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.

ID	Title	Description
OG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
OG001	Part A: 15 mg BI 891065	3 film-coated tablets of 5 mg (15 mg total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Secondary

Part A: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)

Area under the concentration time curve of BI 891065 over a dosing interval at steady state (AUCtau,ss).

Timeframe description:

*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.

**: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanomol * hours per Liter

ID	Title	Description
OG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
OG001	Part A: 15 mg BI 891065	3 film-coated tablets of 5 mg (15 mg total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Secondary

Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

Area under the concentration-time curve of BI 891065 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in the first treatment cycle.

Timeframe description:

*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.

**: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.

Pharmacokinetic Parameter Set (PKS) (Part A): All patients in the TS (Part A) who have at least one valid secondary pharmacokinetic (PK) endpoint available.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanomol * hours per Liter

ID	Title	Description
OG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.
OG001	Part A: 15 mg BI 891065	3 film-coated tablets of 5 mg (15 mg total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.

Primary

Part B: Maximum Tolerated Dose (MTD) of BI 891065 in Combination With Ezabenlimab

Maximum tolerated dose (MTD) of BI 891065 in combination with ezabenlimab, defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.

MTD Evaluation Set (Part B): All patients who received BI 891065 and BI 754091, and completed the safety assessments required during cycle 1 or who experienced a DLT during cycle 1.

Posted

Number

Milligram

First treatment cycle (MTD evaluation period), up to 21 days.

ID	Title	Description
OG000	Part B: BI 891065 + 240mg BI 754091	Film-coated tablets of BI 891065 (dose level 50 mg once daily (QD), 200 mg QD, 400 mg QD or 200 mg twice daily (BID)) were administered orally in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Units	Counts
Participants

Primary

Part B: Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period

DLT is defined as:

MTD Evaluation Set (Part B): All patients who received BI 891065 and BI 754091, and completed the safety assessments required during cycle 1 or who experienced a DLT during cycle 1.

Posted

Number

Participants

First treatment cycle (MTD evaluation period), up to 21 days.

ID	Title	Description
OG000	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Secondary

Part B: Number of Patients With Dose-limiting Toxicities (DLTs) Observed During the Entire Treatment Period

DLT is defined as:

Treated Set (TS) (Part B): The TS (Part B) included all patients who received at least one dose of BI 891065 or BI 754091.

Posted

Count of Participants

Participants

From first drug administration until last drug administration plus residual effect period of 30 days, up to 386 days.

ID	Title	Description
OG000	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Secondary

Part B: Number of Patients With Objective Response (OR)

OR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, defined as the best overall response of complete response (CR) and partial response (PR), where the best overall response is the best time point response recorded from the first administration of study medication until the end of treatment. Number of patients with objective response is reported.

Treated Set (TS) (Part B): The TS (Part B) included all patients who received at least one dose of BI 891065 or BI 754091.

Posted

Count of Participants

Participants

Up to 356 days.

ID	Title	Description
OG000	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
OG001	Part B: 200 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 50 mg, or 2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Secondary

Part B: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

Area under the concentration-time curve of BI 891065 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in the first treatment cycle.

Pharmacokinetic Parameter Set (PKS) (Part B): All patients in the TS (Part B) who have at least one valid secondary pharmacokinetic (PK) endpoint available.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*nanomol / Liter

At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.

ID	Title	Description
OG000	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
OG001	Part B: 200 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 50 mg, or 2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Secondary

Part B: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)

Area under the concentration time curve of BI 891065 over a dosing interval at steady state (AUCtau,ss) in the first treatment cycle.

Pharmacokinetic Parameter Set (PKS) (Part B): All patients in the TS (Part B) who have at least one valid secondary pharmacokinetic (PK) endpoint available. Only patients with available data for this endpoint were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*nanomol/Liter

ID	Title	Description
OG000	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
OG001	Part B: 200 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 50 mg, or 2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Secondary

Part B: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)

Maximum measured plasma concentration of BI 891065 at steady state (Cmax,ss) in the first treatment cycle.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

Nanomol/Liter

ID	Title	Description
OG000	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50 mg of BI 891065 was administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.
OG001	Part B: 200 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 50 mg, or 2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Secondary

Part B: Maximum Measured Plasma Concentration (Cmax) of BI 754091 in the First Treatment Cycle

Maximum measured plasma concentration (Cmax) of BI 754091 in the first treatment cycle.

Results are reported for the overall group only since dose level of BI 754091 is fixed in this trial.

Pharmacokinetic Parameter Set (PKS) (Part B): All patients in the TS (Part B) who have at least one valid secondary pharmacokinetic (PK) endpoint available. As pre-specified in the protocol, the four cohorts in Part B were treated with the same dosage of BI 754091 and analyzed together.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

Microgram/milliliter

Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.

ID	Title	Description
OG000	Part B: 891065 + 240 mg BI 754091 - Overall	Film-coated tablets of BI 891065 (dose level 50 mg once daily (QD), 200 mg QD, 400 mg QD or 20 0mg twice daily (BID)) were administered orally in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Units

Secondary

Part B: Area Under the Concentration-time Curve of BI 754091 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

Area under the concentration-time curve of BI 754091 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in the first treatment cycle.

Results are reported for the overall group only since dose level of BI 754091 is fixed in this trial.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

Hours*micorgram/milliliter

Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.

ID	Title	Description
OG000	Part B: 891065 + 240 mg BI 754091 - Overall	Film-coated tablets of BI 891065 (dose level 50 mg once daily (QD), 200 mg QD, 400 mg QD or 200 mg twice daily (BID)) were administered orally in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A: 5 mg BI 891065	1 film-coated tablet of 5 milligram (mg) of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.	1	3	1	3	3	3
EG001	Part A: 15 mg BI 891065	3 film-coated tablets of 5 mg (15 mg total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.	1	1	0	1	1	1
EG002	Part A: BI 891065 25 mg	1 film-coated tablet of 5mg plus 1 film-coated tablet of 20mg (25mg in total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.	2	3	1	3	3	3
EG003	Part A: BI 891065 50 mg	1 film-coated tablet of 50mg of BI 891065 was administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as they derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.	3	4	1	4	4	4
EG004	Part A: 100 mg BI 891065	2 film-coated tablets of 50 mg (100 mg in total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.	2	3	2	3	3	3
EG005	Part A: 200 mg BI 891065	4 film-coated tablets of 50 mg of BI 891065 (200 mg in total) were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.	1	3	1	3	2	3
EG006	Part A: 400 mg BI 891065	8 film-coated tablets of 50 mg (400 mg in total) of BI 891065 were administered orally once daily in patients with advanced and/or metastatic malignancies. Treatment cycles were 21 days. Patients continued treatment with BI 891065 as long as the derived clinical benefit. (Up to 252 days). Patients were asked to fast overnight, at least 10 hours prior to day 1 and day 15 in cycle 1.	2	8	2	8	8	8
EG007	Part B: 50 mg BI 891065 QD + 240 mg BI 754091	1 film-coated tablet of 50mg of BI 891065 was administered orally once daily (QD) in combination with 240 milliliter (mL) solution for infusion after dilution of BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.	2	6	0	6	6	6
EG008	Part B: 200 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 50 mg, or 2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.	2	14	3	14	13	14
EG009	Part B: 400 mg BI 891065 QD + 240 mg BI 754091	4 film-coated tablets of 100 mg (400 mg total) of BI 891065 were administered orally once daily (QD) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.	0	8	3	8	8	8
EG010	Part B: 200 mg BI 891065 BID + 240 mg BI 754091	2 film-coated tablets of 100 mg (200 mg total) of BI 891065 were administered orally twice daily (BID) in combination with 240 mg BI 754091, administered as intravenous infusion, on day 1 of each treatment cycle. Treatment cycles were 21 days. Patients were allowed to continue treatment with BI 891065 and BI 754091 as long as they derived clinical benefit. (Up to 356 days). Patients were asked to fast overnight, at least 10 hours prior to day 1, day 15 and day 16 in cycle 1.	3	9	2	9	9	9

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG0030 affected4 at risk EG0040 affected3 at risk EG0050 affected3 at risk EG0060 affected8 at risk EG0070 affected6 at risk EG0080 affected14 at risk EG0091 affected8 at risk EG0100 affected9 at risk
Enterovesical fistula	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Oedema peripheral	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Sepsis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Septic shock	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Delirium	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0021 affected3 at risk EG003
Laryngeal haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG0031 affected4 at risk EG0040 affected3 at risk EG0050 affected3 at risk EG0063 affected8 at risk EG0070 affected6 at risk EG0083 affected14 at risk EG0090 affected8 at risk EG0101 affected9 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Periorbital swelling	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Vision blurred	Eye disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected1 at risk EG0021 affected3 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Asthenia	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Chills	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Early satiety	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Facial pain	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	MedDRA 23.1	Systematic Assessment	EG0003 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Gait disturbance	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Influenza like illness	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Malaise	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Mucosal inflammation	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Oedema peripheral	General disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0021 affected3 at risk EG003
Pyrexia	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Swelling	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Bacterial infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Candida infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Escherichia urinary tract infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Localised infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Otitis media	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rash pustular	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rhinitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Sinusitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Anastomotic ulcer	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0021 affected3 at risk EG003
Blood creatinine increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Blood potassium decreased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
International normalised ratio increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Platelet count decreased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Weight decreased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Weight increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0021 affected3 at risk EG003
Hypercreatininaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0021 affected3 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Amnesia	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Presyncope	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Syncope	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Depression	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Scrotal oedema	Reproductive system and breast disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected1 at risk EG0020 affected3 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0021 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003
Phlebitis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected1 at risk EG0020 affected3 at risk EG003

ID	Term
D009369	Neoplasms
D009362	Neoplasm Metastasis
D002289	Carcinoma, Non-Small-Cell Lung

Ancestor Terms

ID	Term
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

Units	Counts
Participants	OG00037

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0101 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0061 affected8 at risk

EG0070 affected6 at risk

EG0081 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0081 affected14 at risk

EG0090 affected8 at risk

EG0101 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0081 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0081 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0051 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0091 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0091 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0041 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0061 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0101 affected9 at risk

EG0041 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0091 affected8 at risk

EG0101 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0101 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0081 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0041 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0091 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0091 affected8 at risk

EG0100 affected9 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0060 affected8 at risk

EG0070 affected6 at risk

EG0080 affected14 at risk

EG0090 affected8 at risk